It is our goal to determine the mechanisms of electrolyte and water secretion by the exocrine pancreas. To accomplish this goal, we will utilize in vivo preparations of both the rabbit and rat pancreas and employ the micro techniques which have been developed in the study of kidney function. 1. We will use the free-flow micropuncture sampling of individual acinar and larger ducts to determine the site and rate at which primary electrolyte secretion takes place and where, how, and if that secretion is modified in the pancreatic duct system. 2. The electrochemical gradient of the various secretion components at various anatomical loci within the pancreatic duct system will be determined using the stopped flow perfusion or split oil drop method, as it is often called. 3. We will make extensive use of microelectrodes to directly measure potential differences, pH and ion activities within the ductal system itself. Particular attention will be paid to the role of divalent cations, principally calcium, on the formation of pancreatic secretions. A special aspect of our study will be measurements of CO2 concentration in situ. These determinations will make possible improved determination of bicarbonate concentrations at specific sites in the ductal system. 4. We will utilize radioisotopic fluxes, perfusion techniques and hormonal stimulation of secretion to aid us in the elucidation of the basic mechanisms of pancreatic electrolyte secretion and its regulation. 5. Concurrent with these studies of the normal pancreatic secretion, we will attempt to develop an animal model of cystic fibrosis of the pancreas and to determine how the secretions of the "diseased" animal differ from the normal.